Effect of intensive therapy on the microvascular complications of type 1 diabetes mellitus

Abstract

The purpose of this report is to summarize and integrate the findings of the Diabetes Control and Complications Trial (DCCT), a randomized controlled clinical trial, and the succeeding observational follow-up of the DCCT cohort in the Epidemiology of Diabetes Interventions and Complications (EDIC) study, regarding the effects of intensive treatment on the microvascular complications of type 1 diabetes mellitus. The DCCT proved that intensive treatment reduced the risks of retinopathy, nephropathy, and neuropathy by 35% to 90% compared with conventional treatment. The absolute risks of retinopathy and nephropathy were proportional to the mean glycosylated hemoglobin (HbA(1c)) level over the follow-up period preceding each event. Intensive treatment was most effective when begun early, before complications were detectable. These risk reductions, achieved at a median HbA(1c) level difference of 9.1% for conventional treatment vs 7.3% for intensive treatment have been maintained through 7 years of EDIC, even though the difference in mean HbA(1c) levels of the 2 former randomized treatment groups was only 0.4% at 1 year (P<.001) (8.3% in the former conventional treatment group vs 7.9% in the former intensive treatment group), continued to narrow, and became statistically nonsignificant by 5 years (8.1% vs 8.2%, P =.09). The further rate of progression of complications from their levels at the end of the DCCT remains less in the former intensive treatment group. Thus, the benefits of 6.5 years of intensive treatment extend well beyond the period of its most intensive implementation. Intensive treatment should be started as soon as is safely possible after the onset of type 1 diabetes mellitus and maintained thereafter, aiming for a practicable target HbA(1c) level of 7.0% or less.

Figures

Figure 1

Comparison of Conventional and intensive Therapy in Cumulative Incidence of Retinopathy Progression and Microalbuminuria Secondary intervention Cohorts Modified from The DCCT Research Group. Cumulative incidence of sustained 3-step progression of 2 cohorts of the Diabetes Control and Complications Trial (DCCT). A, The Early Treatment Diabetic Retinopathy Study scale cohort (conventional vs intensive, P<.001). B, The development of microalbuminuria cohort (conventional vs Intensive, P=.001).

Figure 2

Risk of Retinopathy Progression vs Mean Clycosylated Hemoglobin (HbA1c) and Time in Study Conventional Treatment Group Reprinted with permission from The American Diabetes Association. Absolute risk of retinopathy progression asa function of the updated mean HbA1cdur-ing the study and the follow-up time estimated from a Poisson model in the conventional treatment group of the Diabetes Control and Complications Trial (DCCT).

Figure 3

Distribution of Glycosylated Hemoglobin (HbA1c) According to Original Diabetes Control and Complications Trial (DCCT) Treatment Assignment at DCCT Closeout and in Each Epidemiology of Diabetes Interventions and Complications (EDIC) The box plots represent the 2nd and 3rd quartiles of the distribution; the heavy horizontal lines, the medians; the thin horizontal lines, the means; and the whiskers, the 5th and 95th percentiies. P values are from Wilcoxon rank sum test.

Figure 4

Estimated Cumulative Incidence of Progression of Retinopathy 3 Steps on the ETDRS Scale From the Level at DCCT Closeout Over 7 Years of EDIC ETDRS indicate Early Treatment Diabetic Retinopathy Study; DCCT, Diabetes Control and Complications Trial; and EDIC, Epidemiology of Diabeted Interventions and Complications. At each EDIC year, approximately one fourth of the treatment groups were examined by fundus photography, except for year 4 when approximately 85% were examined. Risk reduction with intensive therapy is 62% (95% confidence interval, 51%-70%; P<.001 the curves show cumulative incidences estimated by a proportional hazards regression model for interval-censored event times that are assumed to follow an underlying weibull distribution. error bars represent confidence intervals.>